Current Stem Cell Research & Therapy - Volume 14, Issue 1, 2019

Background: Periodontitis is an inflammatory disease that can result in destruction of the tooth attachment apparatus. Therefore, periodontal tissue regeneration is currently an important focus of research in the field. Approaches using stem cells and reprogrammed cells, such as induced pluripotent stem cells (iPSCs) or trans-differentiated cells, represent the cutting edge in periodontal regeneration, and have led to many trials for their clinical application. Objectives and Results: In this review, we consider all available stem cell sources, methods to obtain the cells, their capability to differentiate into the desired cells, and the extent of their utilization in periodontal regeneration. In addition, we introduce the new concepts of using iPSCs and transdifferentiated cells for periodontal regeneration. Finally, we discuss the promise of tissue engineering for improving cell therapy outcomes for periodontal regeneration. Conclusions: Despite their limitations, iPSCs and trans-differentiated cells may be promising cell sources for periodontal tissue regeneration. Further collaborative investigation is required for the effective and safe application of these cells in combination with tissue engineering elements, like scaffolds and biosignals.

Cardiovascular disease (CVD) is one of the world-wide healthcare problem that involves the heart or blood vessels. CVD includes myocardial infarction and coronary artery diseases (CAD). Dysfunctional myocardial cells are leading causes of low cardiac output or ventricular dysfunction after cardiac arrest and may contribute to the progression of CVD which could not generate new cardiomyocytes in human adult heart. The mesenchymal stem cells (MSCs) which are present in adult marrow can self-renew and have the capacity of differentiation into multiple types of cells including cardiomyocytes. Recent biochemical analyses greatly revealed that several regulators of MSCs, such as HGF, PDGF, Wnt, and Notch-1 signaling pathways have been shown to be involved in the proliferation and differentiation into cardiomyocytes. Preclinical studies are paving the way for further applications of MSCs in the repair of myocardial infarction. In this study, we discuss and summarize the paracrine mechanisms involved in MSCs differentiation into cardiomyocytes.

Mesenchymal stromal cells (MSCs), characterized by both multidifferentiation potential and potent immunomodulatory capacity, represent a promising, safe and powerful cell based-therapy for repairing tissue damage and/or treating diseases associated with aberrant immune responses. Natural killer (NK) cells are granular lymphocytes of the innate immune system that function alone or in combination with other immune cells to combat both tumors and virally infected cells. After their infusion, MSCs are guided by host inflammatory elements and can interact with different immune cells, particularly those of the innate immune system. Although some breakthroughs have been achieved in understanding these interactions, much remains to be determined. In this review, we discuss the complex interactions between NK cells and MSCs, particularly the importance of improving the therapeutic value of MSCs.

The skin is one of the crucial body organs with anatomy and physiology linked to various disorders including congenital and acquired diseases. Nowadays, mesenchymal stem cell (MSCs)- based therapy has appeared as a promising therapeutic field, in which many see opportunities to cure the costliest and incurable diseases. However, one question to be asked is that if the use of MSCs in clinical trials studies and diseases treatment has improved. In this study, the clinical trials using MSCs in skin diseases were reviewed. A remarkable number of clinical trial studies are in progress in this field; however, only a few of them have led to tangible benefits for patients. The relevant papers and ongoing clinical trials that address MSC's therapeutic goals for various skin disorders were examined. This review can be very useful for both the dermatologists and basic skin researchers interested in contributing to stem cell-based therapeutic researches in the area of skin disorders.

Aging is a key dangerous factor for the occurrence and severity of tendon injury, but the exact cognition of the relationship is elusive at present. More previous studies suggest age-related changes occur at tendon mechanical properties, structure and composition, but the pathological alternations may be overlooked, which might be a cause for the structure and function variations, and even speed up the progress of age-related disorders. Recently, the presence of tendon stem/progenitor cells (TSPCs) would provide new insights for the pathogenesis of tendon aging. In this review, the tendon mechanical properties, structure and composition are presented in brief, then, the pathological changes of the aging tendon are described firstly, and the latest researches on alterations of TSPCs in the pathogenesis of tendon aging have also been analyzed. At a cellular level, the hypothetical model of altered TSPCs fate for tendon aging is also proposed. Moreover, the regulation of TSPCs as a potential way of the therapies for age-related tendon diseases is discussed. Therefore, reversing the impaired function of TSPCs and promoting the tenogenic differentiation of TSPCs could become hot spots for further study and give the opportunity to establish new treatment strategies for age-related tendon injuries.

Mesenchymal Stem Cells [MSCs] are a heterogeneous population of fibroblast-like cells which maintain self-renewability and pluripotency. Many studies have demonstrated the immunomodulatory effects of MSCs on the innate and adaptive immune cells. As a result of interactions with tumor cells, microenvironment and immune-stimulating milieu, MSCs contribute to tumor progression by several mechanisms, including sustained proliferative signal in cancer stem cells [CSCs], inhibition of tumor cell apoptosis, transition to tumor-associated fibroblasts [TAFs], promotion of angiogenesis, stimulation of epithelial-mesenchymal transition [EMT], suppression of immune responses, and consequential promotion of tumor metastasis. Here, we present an overview of the latest findings on Janusfaced roles that MSCs play in the tumor microenvironment [TME], with a concise focus on innate and adaptive immune responses.

In the field of stem cell therapy, research on the application of mesenchymal stem cells (MSCs) has flourished because of the various functions. On the other hand, research on the method of cell transplantation has developed from the administration of cell suspensions to cell-sheet engineering and 3D technology. In the trend, a cell transplantation platform named CellSaic, which is a combination of xeno-free recombinant scaffolds in a cell aggregate-like shape, was developed. CellSaic is the cell transplantation platform that can prevent the central necrosis within cell aggregates by arranging the cells and petaloid pieces of recombinant peptide (RCP) in a mosaic. The prevention of central necrosis is the most significant advantage over other 3D culture systems. This review details the unique characteristics of CellSaic including safety examination results and describes its future application for MSC transplantation. Particularly, in the application of MSCs, it has been reported that the MSC CellSaics increased the effect on improving various symptoms compared with MSCs only in the application of the therapy to inflammatory bowel disease (IBD), cerebral infarction, bone cartilage regeneration in joints, and islet transplantation. In accordance with the “One Health” concept, it is anticipated that this technology is expected to contribute to companion animal therapy and human therapy in the future.

Low back pain (LBP) is one of the world's most common musculoskeletal diseases and is frequently associated with intervertebral disc degeneration (IDD). While the main cause of IDD is commonly attributed to a reduced number of nucleus pulposus (NP) cells, current treatment strategies (both surgical and more conservative) fail to replenish NP cells or reverse the pathology. Cell replacement therapies are an attractive alternative for treating IDD. However, injecting intervertebral disc (IVD) cells, chondrocytes, or mesenchymal stem cells into various animal models of IDD indicate that transplanted cells generally fail to survive and engraft into the avascular IVD niche. Whereas pluripotent stem cells (PSCs), including induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs), hold great potential for revolutionizing regenerative medicine, current protocols for differentiating these cells into NP-like cells are inadequate. Nucleus pulposus progenitor cells (NPPCs), which are derived from the embryonic notochord, can not only survive within the harsh hypoxic environment of the IVD, but they also efficiently differentiate into NP-like cells. Here we provide an overview of the latest progress in repairing degenerated IVDs using PSCs and NPPCs. We also discuss the molecular pathways by which PSCs differentiate into NPPCs in vitro and in vivo and propose a new, in vivo IDD therapy.

Islet cell auto-transplantation is a novel strategy for maintaining blood glucose levels and improving the quality of life in patients with chronic pancreatitis (CP). Despite the many recent advances associated with this therapy, obtaining a good yield of islet infusate still remains a pressing challenge. Reprogramming technology, by making use of the pancreatic exocrine compartment, can open the possibility of generating novel insulin-producing cells. Several lineage-tracing studies present evidence that exocrine cells undergo dedifferentiation into a progenitor-like state from which they can be manipulated to form insulin-producing cells. This review will present an overview of recent reports that demonstrate the potential of utilizing pancreatic ductal cells (PDCs) for reprogramming into insulin- producing cells, focusing on the recent advances and the conflicting views. A large pool of ductal cells is released along with islets during the human islet isolation process, but these cells are separated from the pure islets during the purification process. By identifying and improving existing ductal cell culture methods and developing a better understanding of mechanisms by which these cells can be manipulated to form hormone-producing islet-like cells, PDCs could prove to be a strong clinical tool in providing an alternative beta cell source, thus helping CP patients maintain their long-term glucose levels.